Evidence map›Paper›PMID 40091338›Full record

Trial reportClinical pharmacology and therapeutics2025

Night-Time Chronotherapy with Methylprednisolone Prevents an Acute Rejection in Pediatric Patients with Liver Transplantation: A Randomized Clinical Trial.

Kentaro Ushijima, Yukihiro Sanada, Shinya Otomo, Keiko Ogaki, Taiichi Wakiya, Noriki Okada, Yuta Hirata, Yasuharu Onishi, Yasunaru Sakuma, Yukiyo Wada and 2 more

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in Clinical pharmacology and therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Kentaro UshijimaDivision of Clinical Pharmacology, Jichi Medical University, Tochigi, Japan.ORCID 0000-0003-2637-3916
Yukihiro SanadaDivision of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Tochigi, Japan.ORCID 0000-0003-2456-0400
Shinya OtomoPharmacy of Jichi Medical University Hospital, Tochigi, Japan.
Keiko OgakiPharmacy of Jichi Medical University Hospital, Tochigi, Japan.
Taiichi WakiyaDivision of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Tochigi, Japan.ORCID 0000-0003-3681-7736
Noriki OkadaDivision of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Tochigi, Japan.
Yuta HirataDivision of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Tochigi, Japan.
Yasuharu OnishiDivision of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Tochigi, Japan.
Yasunaru SakumaDivision of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Tochigi, Japan.
Yukiyo WadaDivision of Pharmaceutics, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Yamaguchi, Japan.
Akio FujimuraDivision of Clinical Pharmacology, Jichi Medical University, Tochigi, Japan.ORCID 0000-0002-5160-5777
Koichi MizutaDivision of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Tochigi, Japan.ORCID 0000-0003-4270-4834

Funding

Japan Research Foundation for Clinical Pharmacology
6 · The paper itself

Abstract

While endogenous cortisol secretion rises in the early morning, the number of lymphocytes in the blood is higher at night, thus exhibiting an antiphase pattern to cortisol secretion. Therefore, compared with the daytime, the infiltration of lymphocytes into immune-reactive tissues is enhanced at night. This study aimed to determine whether the administration of methylprednisolone (mPSL) in the evening is more effective against T cell-mediated rejection (TCMR) after liver transplantation compared with morning administration. This study used a randomized, open-label, parallel-group comparison design. Pediatric patients scheduled to undergo living-donor liver transplantation were randomly divided into morning (8:00 a.m.) and evening (8:00 p.m.) mPSL administration groups. The primary endpoint was the occurrence of TCMR within 14 days of surgery. Sixty-two patients were enrolled between 2014 and 2023, and six patients were excluded from the analysis as their dose of mPSL deviated from the protocol within 14 days after surgery. Of the 56 subjects analyzed, TCMR was detected in 10 of the morning group (n = 29) and three of the evening group (n = 27) within 14 days after surgery. Stratified analysis of patients who did not receive preoperative rituximab treatment showed that none of the evening group and 36.4% of the morning group developed TCMR within 14 days after surgery (P < 0.01, 95% confidence interval; 2.00-infinity). Safety evaluation results were comparable between the two groups. This study shows that the evening administration of mPSL is an effective approach for suppressing TCMR. This study is hypothesis generating, and replication in further studies is needed.

Indexed as

Drug ChronotherapyGraft RejectionImmunosuppressive AgentsLiver TransplantationMethylprednisoloneAdolescentChildChild, PreschoolCircadian RhythmFemaleGlucocorticoidsHumansMaleT-LymphocytesTreatment OutcomeGlucocorticoidsImmunosuppressive AgentsMethylprednisolone

Identifiers

PMID40091338
PMCPMC12272322

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.